The optimization of cell guidance through autologous or artificial tissue scaffolds has long been a topic of great interest. The most prevalent and thus far the most successfully applied off-the-shelf “tissue-engineered” products were all originally intended to serve as dermal replacement scaffolds. Commercially available scaffolds are acellular and thus share the common requirements of host cell invasion and vascularization to achieve durable incorporation. Because this process is prolonged, requiring a minimum of several weeks for completion and necessitating obligatory dressing changes, wound immobilization, and nursing care, there is significant interest in developing better scaffolds that could optimize the rate of cellular invasion. (Eppley, Plast Reconstr Surg. 107:757-762 (2001); Wong et al., Plast Reconstr Surg. 121:1144-1152 (2008)).
Currently available acellular dermal replacements can be categorized into two broad groups: products derived from decellularized dermis, and synthetic products based on naturally-derived hydrogels (Truong et al. J. Burns Wounds 4:e4 (2005)).
Commercially available decellularized dermal products are made of decellularized cadaveric porcine or human dermis. As a result of the decellularization process, these products contain an internal network of microchannels with an intact basement membrane that are the remnants of the native dermal microvasculature.
INTEGRA (Integra LifeSciences, Plainsboro, N.J.), another commonly applied dermal regeneration template, is comprised of a synthetic “dermal” porous layer of cross-linked type I bovine collagen and chondroitin-6-sulfate covered by an “epidermal” semi-permeable silicone sheet. Following implantation, the silicone sheet is replaced with split-thickness autograft once the dermal layer has vascularized (Yannas et al., Science 215:174-176 (1982)). Unlike decellularized dermal products, INTEGRA is representative of products without an internal vascular structure and is instead characterized by its random porosity (mean pore diameter 30-120 μm) (van der Veen et al., Burns 36:305-321 (2010)).
The use of currently available tissue replacement scaffolds is not without substantial associated cost. For example, the production of decellularized dermal products requires tissue acquisition and harvesting, as well as decellularization and sterilization processes (Ng et al., Biomaterials 25:2807-2818 (2004)). In addition, commercially available tissue scaffolds are avascular and prone to high failure rates when used in complex settings, such as irradiated wounds or those with exposed hardware or bone. In such complex settings, neovascularization is insufficient using existing tissue replacement products.
Improved tissue scaffolds that promote optimal cellular invasion and vascularization of new and surrounding tissue are highly desired in the art.